As the foundation for developing strategies for gene and immunotherapy of neoplasms affecting human communication, research has focused on the identification of immune recognition determinants, components of the inflammatory response and cytokines in the environment of developing squamous cell neoplasms of the upper aerodigestive tract. Immune and in situ reverse transcription-polymerase chain reaction histochemistry is being used to define the cell types present in the tumor environment and the expression of gene products involved in immunity. Three cytokines involved in immune regulation are expressed and secreted by squamous cell carcinoma cell lines and their expression in situ has been determined. Future studies employing the transfer of genes encoding these cytokines to nonexpressing murine tumor lines will determine if the cytokines identified play a role in tumor pathogenesis and progression. Gene transfer of selected cytokine and recognition determinants which may promote protective helper and cytolytic T lymphocyte immunity to squamous cell carcinoma are being tested in experimental tumor models. Preliminary evidence indicates that 3 cytokines involved in the T helper type 1 and T cytolytic T cell response have activity against murine squamous cell carcinoma and induce partial response in vivo. The basis for an incomplete response is now being explored in an attempt to optimize immune stimulation and determine the nature of the immune response.